1. Field of the Invention
The present invention relates generally to the field of immunology. More particularly, it concerns preventative and therapeutic compositions and methods that inhibit stimulation of the immune system.
2. Description of Related Art
While stimulation of the immune systems prevents and controls infection, it can have an adverse physiological effect, as is the case with autoimmune diseases and phenomena, with rejection of cells and tissues during adoptive immunotherapy and transplants, and with invasions by pathogens. Inhibition of this stimulation can have beneficial therapeutic results. However, new and more effective treatments to effect inhibition of immunostimulation are still needed.
Autoimmunity is generally caused by aberrations in lymphocyte activities. While the precise cause of autoimmunity is not known, it most likely involves a mechanistic failure in at least one of the steps of maintaining self-tolerance to the body""s own antigens. Several factors are thought to play a part in the development of autoimmunity, including the host""s genetic makeup. Autoimmune diseases afflict approximately 1% to 2% of the human population. Autoimmune phenomena, are the result of a disease, for example myocardial infarcation, that may cause damage to tissue, which consequently effects the release of immunogenic tissue antigens; this condition, unlike autoimmune disease, is unrelated to the pathogenesis of the disease that caused it.
There are a wide variety of autoimmune diseases. They are classified as either organ-specific based on the primary site of injury or systemic (see Table 1). There are three ways in which damage or injury to tissue is caused by autoimmune disease: cell-mediated immunity, cell lysis and autoantibody-induced release of inflammatory mediators, and immune complex disease.
Cell-mediated immunity occurs when sensitized T cells directly damage cells or release lymphokines that augment the inflammatory reaction. An association of an autoantibody with its antigen in intercellular fluid causes cell lysis and autoantibody-induced release of inflammatory mediators. This interaction results in release of inflammatory mediators, induction of the complement pathway, or activation of cytotoxic cells, which can trigger cell lysis. The third mechanism, immune complex disease, involves a reaction between circulating autoantibodies and antigens on the cell surface. This complex becomes deposited in tissue such as the joints, blood vessels, and glomeruli, causing complement to be fixed and subsequent inflammation and tissue damage.
Rejection of cells and tissue can involve rejection of the graft by the host. The body""s own cells are identified as self because of a complex series of cell surface molecules known as major histocompatibility molecules (MHC). Rejection of cells and tissues can occur following transplantation of cells or organs or after adoptive immunotherapy has been implemented. In graft-versus host disease (GVHD), the grafted immune system attacks the host cells. One example in which GVHD becomes particularly significant is bone marrow transplantation (BMT), which is frequently used for the treatment of a variety of bone marrow-related disorders and in cancer therapy to replace bone marrow cells lost to chemotherapy and radiation treatment. In severe cases of GVHD, a patient""s compromised immune system gives rise to many complications including those in the liver, causing jaundice, in the skin causing rash, and in the gastrointestinal tract, including diarrhea, anorexia, nausea and vomiting, malabsorption, abdominal pain ileus, and ascites formation.
Sepsis is the primary cause of death in the intensive care unit with more than 400,000 cases in the United States annually. It can be caused by infection by a pathogen, such as viruses, bacteria, fungi, and parasites, which triggers host defenses. This may result in activation of innate immunity, particularly, an inflammatory response, which consequently promotes deleterious effects (collectively termed xe2x80x9csepsisxe2x80x9d) including shock, respiratory distress, capillary leaks, renal failure, jaundice, bleeding, coma and death.
Despite this information, preventative and therapeutic treatment to inhibit stimulation of the immune system is still needed. Oligodeoxynucleotides (ODN), bacterial DNA, and phosphorothioate oligodeoxynucleotides with unmethylated CpG-motifs are immunostimulatory and may contribute to autoimmunity. Thus, they can serve as a model system to identify compounds and methods that effect inhibition of immunostimulation. Using CpG-ODN, a number of compounds have been identified as possessing this property. For example, a number of quinoline derivatives that are active against stimulation by CpG-ODN have been shown to induce remission of rheumatoid arthritis and lupus erythematosus (Fox, 1993; Wallace, 1994). Chloroquine and a number of structural analogs specifically and powerfully inhibit this effect at nanomolar concentration. Therefore, inhibition of CpG-ODN immunostimulation can be effected generally in the treatment of autoimmune diseases and phenomena, sepsis, and transplantation rejection, including graft-versus-host disease.
The inhibition of immune stimulation in cases such as autoimmune diseases, tissue transplantation and the like would be therapeutically beneficial. Currently, methods to inhibit stimulation of the immune system are limited. Therefore, it is a goal of the present invention to provide methods and compositions for inhibiting immunostimulation in a subject.
In one embodiment of the invention, a method of inhibiting immunostimulation in a subject by administering an effective amount of a substituted 4-quinolinamine composition to the subject comprising a compound having the structural formula A is provided. 
A substituted 4-quinolinamine composition of formula A, comprises groups RA, RB, R2, R3, R5, R6, R7 and R8, wherein RA is hydrogen atom or a lower alkyl group, RB is a substituted or unsubstituted alkyl, alkenyl or alkynyl secondary or tertiary amine, R2 is a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group, an substituted or unsubstituted anthracyl group, a substituted or unsubstituted phenanthryl group or a substituted or unsubstituted styryl group, R3 is a hydrogen atom, R5 is a hydrogen atom, R6 is a hydrogen atom or a halogen atom, R7 is a hydrogen atom or a halogen atom, R8 is a hydrogen atom and pharmaceutically acceptable salts thereof. In preferred embodiments, the R2 phenyl, naphthyl, anthracyl, styryl or phenanthryl group substitution further comprise one or more substitutions selected from the group consisting of an alkyl group, an alkoxy group, an alkoxyalkyl group, an ester group, an alkylamino group, a dialkylamino group, a cyclic amino group, a halogen atom, and any combination thereof. In some aspects of the invention, the R2 substitution is an N-substituted aminomethyl group, a cyclic aminomethyl group, or an aminomethyl group, additionally substituted at the nitrogen atom with a cyclic aminoalkyl group. In particularly preferred embodiments, a cyclic amino group is a piperazino group, a piperidino group, a pyrrolidino group, an imidazolyl group, a pyridyl, or a morpholino group. In another embodiment, the RB substituted alkyl is selected from the group consisting of a cyclic amino group, furyl, thienyl, phenyl, alkylamino group, dialkylamino group, and any combination thereof. It is contemplated that phenyl includes a substituted phenyl. In preferred embodiments, a cyclic amino group is a piperazino group, a piperidino group, a pyrrolidino group, an imidazolyl group, a pyridyl group, or a morpholino group. The cyclic amino groups in RB or R2 may be further substituted with an alkyl group, for example, an N-methylpiperazino or an N-pyrrolidinoalkyl. It is further contemplated that there is a covalent bond formed between RA and RB, for example, to form an N-methylpiperazino.
In another embodiment, the present invention provides a method of inhibiting immunostimulation in a subject comprising administering an effective amount of a substituted 4-quinolinamine composition to said subject comprising a compound having the structural formula B. 
A substituted 4-quinolinamine composition of formula B, comprises a phenyl group, R2, R3, R5, R6, R7 and R8, wherein R2 is a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group, a substituted or unsubstituted anthracyl group, a substituted or unsubstituted styryl group or a substituted or unsubstituted phenanthryl group, R3 is a hydrogen atom, R5 is a hydrogen atom, R6 is a hydrogen atom or a halogen atom, R7 is a hydrogen atom, a halogen atom or an alkyl halogen atom, R8 is a hydrogen atom and pharmaceutically acceptable salts thereof. In a preferred embodiment, when the R2 phenyl, naphthyl, anthracyl, styryl or phenanthryl group comprises substitutions, these are defined as one or more substitutions selected from the group consisting of an alkyl group, an alkoxy group, an alkoxyalkyl group, an ester group, an alkylamino group, an dialkylamino group, a cyclic amino group, a halogen atom or any combination thereof. In particularly preferred embodiments, a cyclic amino group is a piperazino group, a piperidino group, a pyrrolidino group, an imidazolino group or a morpholino group.
The phenyl group additionally may be substituted at positions R9, R10, R11, R12 and R13, wherein the substituted phenyl group comprises one or more substitutions selected from the group consisting of an alkyl group, an alkoxy group, an alkoxyalkyl group, an ester group, an alkylamino group, an dialkylamino group, a cyclic amino group, a furan group, a thiophene group, a halogen atom or any combination thereof. In preferred embodiments, a cyclic amino group is a piperazino group, a piperidino group, a pyrrolidino group, an imidazolino group or a morpholino group.
In further embodiments of the invention, a method of inhibiting immunostimulation in a subject comprises administering an effective amount of a substituted 4-quinolinamine composition to the subject comprising a compound having the structural formula C. 
A substituted 4-quinolinamine composition of formula C, comprises a phenyl group spatially distanced form the quinolinamine by an alkyl group of 0 to 4 CH2 molecules, R2, R3, R5, R6, R7 and R8, wherein R2 is a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group, a substituted or unsubstituted anthracyl group, a substituted or unsubstituted styryl group or a substituted or unsubstituted phenanthryl group, R3 is a hydrogen atom, R5 is a hydrogen atom, R6 is a hydrogen atom or a halogen atom, R7 is a hydrogen atom, a halogen atom or an alkyl halogen atom, R8 is a hydrogen atom and pharmaceutically acceptable salts thereof. In se preferred embodiments, the R2 phenyl, naphthyl, anthracyl, styryl or phenanthryl group substitution comprises one or more substitutions selected from the group consisting of an alkyl group, an alkoxy group, an alkoxyalkyl group, an ester group, an alkylamino group, an dialkylamino group, a cyclic amino group, a halogen atom or any combination thereof. In particularly preferred embodiments, a cyclic amino group is a piperazino group, a piperidino group, a pyrrolidino group, an imidazolino group or a morpholino group.
In other embodiments of the invention, the phenyl group additionally may be substituted at positions R9, R10, R11, R12 and R13, wherein the substituted phenyl group comprises one or more substitutions selected from the group consisting of an alkyl group, an alkoxy group, an alkoxyalkyl group, an ester group, an alkylamino group, an dialkylamino group, a cyclic amino group, a furan group, a thiophene group, a halogen atom, or any combination thereof.
In another embodiment, a method of inhibiting immunostimulation in a subject comprises administering an effective amount of a substituted bis-4-quinolinamine composition to the subject comprising a compound having the structural formula D. 
A substituted bis-4-quinolinamine composition having the structural formula D, comprises RB on the first 4-quinolinamine covalently attached to RBxe2x80x2 on the second 4-quinolinamine by linker group Y, R2 is a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group, a substituted or unsubstituted anthracyl up, a substituted or unsubstituted styryl group or a substituted or unsubstituted phenanthryl group, R3 is a hydrogen atom, R5 is a hydrogen atom, R6 is a hydrogen atom or a halogen atom, R7 is a hydrogen atom or a halogen atom, R8 is a hydrogen atom, R2xe2x80x2 is a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group, an substituted or unsubstituted anthracyl group, a substituted or unsubstituted styryl group or a substituted or unsubstituted phenanthryl group, R3xe2x80x2 is a hydrogen atom, R5xe2x80x2 is a hydrogen atom, R6xe2x80x2 is a hydrogen atom or a halogen atom, R7xe2x80x2 is a hydrogen atom or a halogen atom, R8xe2x80x2 is a hydrogen atom and pharmaceutically acceptable salts thereof. In other embodiments, the R2 phenyl, naphthyl, anthracyl, styryl or phenanthryl group substitution is further defined as one or more substitutions selected from the group consisting of an alkyl group, an alkoxy group, an alkoxyalkyl group, an ester group, an alkylamino group, an dialkylamino group, a cyclic amino group, a halogen atom or any combination thereof and the R2xe2x80x2 phenyl, naphthyl, anthracyl, styryl or phenanthryl group substitution is further defined as one or more substitutions selected from the group consisting of an alkyl group, an alkoxy group, an alkoxyalkyl group, an ester group, an alkylamino group, an dialkylamino group, a cyclic amino group, a halogen atom or any combination thereof.
In preferred embodiments, a cyclic amino group is a piperazino group, a piperidino group, a pyrrolidino group, an imidazolino group or a morpholino group. In particular embodiments, the linker group Y is an alkyl group, an ester group, an alkoxyalkyl group, an alkylamino group, an dialkylamino group, amido group, a cyclohexane, an piperazino group or any combination thereof.
In other embodiments of the present invention, a method of inhibiting immunostimulation in a subject comprising administering an effective amount of a substituted bis-9-aminoacridine composition to the subject, comprising a compound 
having the structural formula E, is provided.
A substituted bis-9-aminoacridine of formula E, comprises RB on the first 9-aminoacridine covalently attached to RBxe2x80x2 on the second 9-aminoacridine by linker group Y. A substituted bis-9-aminoacridine of formula E further comprises OR2, OR2xe2x80x2, R3, R3xe2x80x2, X and Xxe2x80x2, wherein OR2 is a lower alkyl group, OR2xe2x80x2 is a lower alkyl group, R3 is a hydrogen atom or a lower alkoxy group, R3xe2x80x2 is a hydrogen atom or a lower alkoxy group, X is a halogen atom, Xxe2x80x2 is a halogen atom and pharmaceutically acceptable salts thereof. In other embodiments, the linker group Y is an alkyl group, an ester group, an alkoxyalkyl group, an alkylamino group, an dialkylamino group, amido group, a cyclohexane, an piperazino group or any combination thereof.
In yet another embodiment, a method of inhibiting immunostimulation in a subject comprises administering an effective amount of a composition to a subject comprising a compound having the structural formula F, wherein a 4-quinolinamine at position RB is covalently linked to a 9-aminoacridine at position RB, by linker group Y. 
The 4-quinolinamine, 9-aminoacridine composition of formula F comprises RA, RB, R2, R3, R5, R6, R7, R8, RBxe2x80x2, OR2xe2x80x2, R3xe2x80x2 and X, wherein RA is atom or a lower alkyl group, R2 is a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group, an substituted or unsubstituted anthracyl group, a substituted or unsubstituted styryl group or a substituted or unsubstituted phenanthryl group, R3 is a hydrogen atom, R5 is a hydrogen atom, R6 is a hydrogen atom or a halogen atom, R7 is a hydrogen atom or a halogen atom, R8 is a hydrogen atom, OR2xe2x80x2 is a lower alkyl group, R3xe2x80x2 is a hydrogen atom, or a lower alkoxy group, X is a halogen atom and pharmaceutically acceptable salts thereof. In certain embodiments, the R2 phenyl, naphthyl, anthracyl, styryl or phenanthryl group substitution is further defined as one or more substitutions selected from the group consisting of an alkyl group, an alkoxy group, an alkoxyalkyl group, an ester group, an alkylamino group, an dialkylamino group, a cyclic amino group, a halogen atom or any combination thereof. In preferred embodiments, a cyclic amino group is a piperazino group, a piperidino group, a pyrrolidino group, an imidazolino group or a morpholino group. In other embodiments, the Y linker is an alkyl group, an ester group, an alkoxyalkyl group, an alkylamino group, an dialkylamino group, amido group, a cyclohexane, an piperazino group or any combination thereof.
In other embodiments of the present invention, 4-quinolinamine and 9-aminoacridine compositions are provided. Thus, in one embodiment, a substituted 4-quinolinamine composition having the structural formula A is provided. 
RA is hydrogen atom or a lower alkyl group, RB is a substituted or unsubstituted alkyl, alkenyl or alkynyl secondary or tertiary amine, R2 is a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group, an substituted or unsubstituted anthracyl group, a substituted or unsubstituted phenanthryl group or a substituted or unsubstituted styryl group, R3 is a hydrogen atom, R5 is a hydrogen atom, R6 is a hydrogen atom or a halogen atom, R7 is a hydrogen atom or a halogen atom, R8 is a hydrogen atom and pharmaceutically acceptable salts thereof. In particular embodiments, the R2 phenyl, naphthyl, anthracyl, styryl or phenanthryl group substitution is further defined as one or more substitutions selected from the group consisting of an alkyl group, an alkoxy group, an alkoxyalkyl group, an ester group, an alkylamino group, a dialkylamino group, a cyclic amino group, a halogen atom and any combination thereof. In preferred embodiments the cyclic amino group is a piperazino group, a piperidino group, a pyrrolidino group, a imidazolino group or a morpholino group. In yet other embodiments, the RB alkyl substitution is selected from the group consisting of a cyclic amino group, furan and thiophene, wherein the cyclic amino group is a piperazino group, a piperidino group, a pyrrolidino group, an imidazolino group or a morpholino group.
In other embodiments of the present invention a substituted 4-quinolinamine composition is provided having the structural formula B. 
The phenyl group can be substituted at R9, R10, R11, R12 and R13, wherein a substituted phenyl group comprises one or more substitutions selected from the group consisting of an alkyl group, an alkylaminoalkyl group, an alkoxy group, an alkoxyalkyl group, an ester group, an alkylamino group, an dialkylamino group, a cyclic amino group, a furan group, a thiophene group, a halogen atom or any combination thereof. R2 is a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group, a substituted or unsubstituted anthracyl group, a substituted or unsubstituted styryl group or a substituted or unsubstituted phenanthryl group, R3 is a hydrogen atom, R5 is a hydrogen atom, R6 is a hydrogen atom or a halogen atom, R7 is a hydrogen atom, a halogen atom or an alkyl halogen atom, R8 is a hydrogen atom and pharmaceutically acceptable salts thereof. In other embodiments, a cyclic amino group is a piperazino group, a piperidino group, a pyrrolidino group, an imidazolino group or a morpholino group.
In yet other embodiments, the R2 phenyl, naphthyl, anthracyl, styryl or phenanthryl group substitution is further defined as one or more substitutions selected from the group consisting of an alkyl group, an alkoxy group, a hydroxy group, an alkoxyalkyl group, an ester group, an alkylamino group, an dialkylamino group, a cyclic amino group, a halogen atom or any combination thereof. In certain embodiments, a cyclic amino group is a piperazino group, a piperidino group, a pyrrolidino group, an imidazolino group or a morpholino group.
In particular embodiments, a substituted 4-quinolinamine composition having the structural formula C is provided. 
The phenyl group can be unsubstituted or substituted at R9, R10, R11, R12 and R13, wherein the substituted phenyl group is distanced spatially from the quinolinamine by an alkyl group of 0 to 4 CH2 and comprises one or more substitutions selected from the group consisting of an alkyl group, an alkoxy group, an alkoxyalkyl group, an ester group, an alkylamino group, an dialkylamino group, a cyclic amino group, a furan group, a thiophene group, a halogen atom, or any combination thereof. R2 is a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group, a substituted or unsubstituted anthracyl group, a substituted or unsubstituted styryl group or a substituted or unsubstituted phenanthryl group, R3 is a hydrogen atom, R5 is a hydrogen atom, R6 is a hydrogen atom or a halogen atom, R7 is a hydrogen atom, a halogen atom or an alkyl halogen atom, R8 is a hydrogen atom and pharmaceutically acceptable salts thereof. In certain embodiments, a cyclic amino group is a piperazino group, a piperidino group, a pyrrolidino group, an imidazolino group or a morpholino group.
In other embodiments, the R2 phenyl, naphthyl, anthracyl, styryl or phenanthryl group substitution is further defined as one or more substitutions selected from the group consisting of an alkyl group, an alkoxy group, an alkoxyalkyl group, an ester group, an alkylamino group, an dialkylamino group, a cyclic amino group, a halogen atom or any combination thereof. In yet other embodiments, a cyclic amino group is a piperazino group, a piperidino group, a pyrrolidino group, an imidazolino group or a morpholino group.
In another embodiment of the invention, a substituted bis-4-quinolinamine composition having the structural formula D is provided. 
The RB on the first 4-quinolinamine is covalently attached to RBxe2x80x2 on the second 4-quinolinamine by linker group Y, wherein linker Y is an alkyl group, an ester group, an alkoxyalkyl group, an alkylaminoalkyl group, an alkylamino group, an dialkylamino group, amido group, a cyclohexane, an piperazino group or any combination thereof. R2 is a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group, a substituted or unsubstituted anthracyl group, a substituted or unsubstituted styryl group or a substituted or unsubstituted phenanthryl group, R3 is a hydrogen atom, R5 is a hydrogen atom, R6 is a hydrogen atom or a halogen atom, R7 is a hydrogen atom or a halogen atom, R8 is a hydrogen atom, R2xe2x80x2 is a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group, an substituted or unsubstituted anthracyl group, a substituted or unsubstituted styryl group or a substituted or unsubstituted phenanthryl group, R3xe2x80x2 is a hydrogen atom, R5xe2x80x2 is a hydrogen atom, R6xe2x80x2 is a hydrogen atom or a halogen atom, R7xe2x80x2 is a hydrogen atom or a halogen atom, R8xe2x80x2 is a hydrogen atom and pharmaceutically acceptable salts thereof.
In certain embodiments, the R2 phenyl, naphthyl, anthracyl, styryl or phenanthryl group substitution is further defined as one or more substitutions selected from the group consisting of an alkyl group, an alkoxy group, an alkoxyalkyl group, a hydroxy group, an ester group, an alkylamino group, an dialkylamino group, a cyclic amino group, a halogen atom or any combination thereof. In preferred embodiments, a cyclic amino group is a piperazino group, a piperidino group, a pyrrolidino group, an imidazolino group or a morpholino group. In other embodiments, the R2xe2x80x2 phenyl, naphthyl, anthracyl, styryl or phenanthryl group substitution is further defined as one or more substitutions selected from the group consisting of an alkyl group, an alkoxy group, a hydroxy group, an alkoxyalkyl group, an ester group, an alkylamino group, an dialkylamino group, a cyclic amino group, a halogen atom or any combination thereof. In particular embodiments, a cyclic amino group is a piperazino group, a piperidino group, a pyrrolidino group, an imidazolino group or a morpholino group.
In certain embodiments, a substituted bis-9-aminoacridine composition having the structural formula E is provided. 
The RB on the first 9-aminoacridine is covalently attached to RBxe2x80x2 on the second 9-aminoacridine by linker group Y, wherein linker Y is an alkyl group, an ester group, an ether group, an alkylamino group, an dialkylamino group, amido group, a cyclohexane, an piperazino group or any combination thereof. OR2 is a lower alkyl group, OR2xe2x80x2 is a lower alkyl group, R3 is a hydrogen atom or a lower alkoxy group, R3xe2x80x2 is a hydrogen atom or a lower alkoxy group, X is a halogen atom, Xxe2x80x2 is a halogen atom and pharmaceutically acceptable salts thereof.
In another embodiment, 4-quinoliamine, 9-aminoacridine composition having the structural formula F is provided. 
The RB position on the 4-quinoliamine is covalently attached to the RBxe2x80x2 position of the 9-aminoacridine by linker Y, wherein linker Y is an alkyl group, an ester group, an alkoxyalkyl group, an alkylamino group, amido group, a cyclohexanedieyl, an piperazino group or any combination thereof. RA is hydrogen atom or a lower alkyl group, R2 is a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group, an substituted or unsubstituted anthracyl group, a substituted or unsubstituted styryl group or a substituted or unsubstituted phenanthryl group, R3 is a hydrogen atom, R5 is a hydrogen atom, R6 is a hydrogen atom or a halogen atom, R7 is a hydrogen atom or a halogen atom, R8 is a hydrogen atom, OR2xe2x80x2 is a lower alkyl group, R3xe2x80x2 is a hydrogen atom, or a lower alkoxy group, X is a halogen atom and pharmaceutically acceptable salts thereof.
In particular embodiments, the R2 phenyl, naphthyl, anthracyl, styryl or phenanthryl group substitution is further defined as one or more substitutions selected from the group consisting of an alkyl group, an alkoxy group, an alkoxyalkyl group, an ester group, an alkylamino group, an dialkylamino group, a cyclic amino group, a halogen atom or any combination thereof. In certain embodiments, a cyclic amino group is a piperazino group, a piperidino group, a pyrrolidino group, an imidazolino group or a morpholino group.
It is also contemplated in the present invention that various other substitutions, such as hydroxy groups and various substituted alkyl groups can be made at the RB and R2 positions of the substituted 4-quinoliamine.
The term xe2x80x9clower alkylxe2x80x9d in the context of the present invention represents straight and branched alkyl groups up to 7 carbon atoms. As used herein the specification, xe2x80x9caxe2x80x9d or xe2x80x9canxe2x80x9d may mean one or more. As used herein in the claim(s), when used in conjunction with the word xe2x80x9ccomprising,xe2x80x9d the words xe2x80x9caxe2x80x9d or xe2x80x9canxe2x80x9d may mean one or more than one. As used herein xe2x80x9canotherxe2x80x9d may mean at least a second or more.
Other objects, features and advantages of the present invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.